Allergenic Extract Sterile Diluent
Name: Allergenic Extract Sterile Diluent
- Allergenic Extract Sterile Diluent injection
- Allergenic Extract Sterile Diluent made from
- Allergenic Extract Sterile Diluent usual dose
- Allergenic Extract Sterile Diluent drug
- Allergenic Extract Sterile Diluent dosage
Allergenic extract is intended for use by, or under the guidance of, physicians who are experienced in the administration of allergenic extracts for diagnosis and/or immunotherapy and the emergency care of anaphylaxis. This extract is not directly interchangeable with other allergenic extracts. The initial dose must be based on skin testing as described in the “DOSAGE AND ADMINISTRATION” section of this insert. Patients switching from other types of extracts to Antigen Laboratories’ allergenic extracts should be started as if they were undergoing treatment for the first time. Patients being switched from one lot of extract to another from the same manufacturer should have the dose reduced by 75%.
Severe systemic reactions may occur with all allergenic extracts. In certain individuals, especially in steroid-dependent/unstable asthmatics, these life-threatening reactions may result in death. Patients should be observed for at least 20 minutes following allergenic extract injections. Treatment and emergency measures, as well as personnel trained in their use, must be available in the event of a life-threatening reaction. Sensitive patients may experience severe anaphylactic reactions resulting in respiratory obstruction, shock, coma and/or death. Report serious adverse events to MedWatch, 5600 Fishers Lane, Rockville, MD 20852-9787, phone 1-800-FDA-1088.
This product should not be injected intravenously. Deep subcutaneous routes have proven to be safe. See the “WARNINGS”, “PRECAUTIONS”, “ADVERSE REACTIONS” and “OVERDOSAGE” sections.
Patients receiving beta-blockers may not be responsive to epinephrine or inhaled bronchodilators. Respiratory obstruction not responding to parenteral or inhaled bronchodilators may require theophylline, oxygen, intubation and the use of life support systems. Parenteral fluid and/or plasma expanders may be utilized for treatment of shock. Adrenocorticosteroids may be administered parenterally or intravenously. Refer to “WARNINGS”, “PRECAUTIONS” and “ADVERSE REACTIONS” sections below.
Allergenic Extract Sterile Diluent Description
Antigen Laboratories’ allergenic extracts are manufactured from source material listed on the vial label. Lower concentrations (e.g. 1:50, 1:33, etc.) may be prepared either by dilution from a more concentrated stock or by direct extraction. The extract is a sterile solution containing extractables of source materials obtained from biological collecting and/or processing firms and Antigen Laboratories. All source materials are inspected by Antigen Laboratories’ technical personnel in accordance with 21 CFR 680.1 (b) (1). The route of administration for immunotherapy is subcutaneous. The routes of administration for diagnostic purposes are intradermal or prick-puncture of the skin.
FOR ALLERGENIC EXTRACTS CONTAINING 50% V/V GLYCERINE AS PRESERVATIVE AND STABILIZER:
Water for Injection…………………………………………………q.s. to volume
Active allergens are described by common and scientific name on the stock concentrate container label or on last page of this circular.
Food allergenic extracts may be manufactured on a weight/volume (w/v) or volume/volume (v/v) basis. Food extracts made from dried raw material are extracted at 2-10% (1:50-1:10 w/v ratio) in extracting fluid containing 50% glycerine. Slurries of juicy fruits or vegetables (prepared with a minimum amount of water for injection) are combined with an equal volume of glycerine for a ration of 1:1 volume/volume (v/v). Sodium chloride and sodium bicarbonate are added to the slurry and glycerine mixture. Fresh egg white extract is prepared by adding one part raw egg white to nine parts of extracting fluid (1:9 v/v).
Antigen E is considered the most important allergen of Short Ragweed pollen and is used for the standardization of Short Ragweed allergenic extracts. Stock mixtures containing Short Ragweed are analyzed for Antigen E content by radial immunodiffusion using Center for Biologics Evaluation and Research (CBER) references and anti-serum. Antigen E content expressed as units of Antigen E per milliliter (U/ml) is printed on container label.
Do not administer in the presence of diseases characterized by bleeding diathesis. Individuals with autoimmune disease may be at risk of exacerbating symptoms of the underlying disease, possibly due to routine immunization. Patients who have experienced a recent myocardial infarction may not be tolerant of immunotherapy. Children with nephrotic syndrome probably should not receive injections due to immunization causing exacerbation of nephrotic disease.
Immunotherapy must be given under physician’s supervision. Sterile solutions, vials, syringes, etc. must be used. Aseptic technique must be observed in making dilutions from stock concentrates. The usual precautions in administering allergenic extracts are necessary, refer to boxed WARNINGS and “WARNINGS” section. Sterile syringe and needle must be used for each individual patient to prevent transmission of serum hepatitis, Human Immunodeficiency Virus (HIV) and other infectious agents.
Epinephrine 1:1000 should be available. Refer to “OVERDOSAGE” section for description of treatment for anaphylactic reactions.
Information for Patients:
Patient should remain under observation of a nurse, physician, or personnel trained in emergency measures for at least 20 minutes following immunotherapy injection. Patient must be instructed to report any adverse reactions that occur within 24 hours after injection. Possible adverse reactions include unusual swelling and/or tenderness at injection site, rhinorrhea, sneezing, coughing, wheezing, shortness of breath, nausea, dizziness, or faintness. Immediate medical attention must be sought for reactions that occur during or after leaving physician’s office.
Carcinogenesis, Mutagenesis, Impairment of Fertility:
Long term studies in animals have not been conducted with allergenic extract to determine their potential for carcinogenicity, mutagenicity or impairment of fertility.
Pregnancy Category C:
Animal reproduction studies have not been conducted with allergenic extracts. It is not known whether allergenic extracts cause fetal harm during pregnancy or affect reproductive capacity. A systemic reaction to allergenic extract could cause uterine contractions leading to spontaneous abortion or premature labor. Allergenic extracts should be used during pregnancy only if potential benefit justifies potential risk to fetus.11
It is not known whether allergenic extracts are excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when allergenic extracts are administered to a nursing woman.
Allergenic extracts have been used routinely in children, and no special safety problems or specific hazards have been found. Children can receive the same dose as adults. Discomfort is minimized by dividing the dose in half and administering injection at two different sites.16, 17
Antihistamines. Antihistamines inhibit the wheal and flare reaction. The inhibitory effect of conventional antihistamines varies from 1 day up to 10 days, according to the drug and patient’s sensitivity. Long acting antihistamines (e.g., astemizole) may inhibit the wheal and flare for up to forty days.1, 2
Imipramines, phenothiazines, and tranquilizers. Tricyclic antidepressants exert a potent and sustained decrease of skin reactions to histamine. This effect may last for a few weeks. Tranquilizers and antiemetic agents of the phenothiazine class have H1 antihistaminic activity and can block skin tests.1
Corticosteroids. Short-term (less than 1 week) administration of corticosteroids at the therapeutic doses used in asthmatic patients does not modify the cutaneous reactivity to histamine, compound 48/80, or allergen. Long-term corticosteroid therapy modifies the skin texture and makes the interpretation of immediate skin tests more difficult.1
Theophylline. It appears that theophylline need not be stopped prior to skin testing.1
Beta-Blockers. Patients receiving beta-blockers may not be responsive to epinephrine or inhaled bronchodilators. The following are commonly prescribed beta-blockers: Levatol, Lopressor, Propanolol Intersol, Propanolol HCL, Blocadren, Propanolol, Inderal-LA, Visken, Corgard, Ipran, Tenormin, Timoptic. Ophthalmic beta-blockers: Betaxolol, Levobunolol, Timolol, Timoptic. Chemicals that are beta-blockers and may be components of other drugs: Acebutolol, Atenolol, Esmolol, Metoprolol, Nadolol, Penbutolol, Pindolol, Propanolol, Timolol, Labetalol, Carteolol.1
Beta-adrenergic agents. Inhaled beta2 agonists in the usual doses used for the treatment of asthma do not usually inhibit allergen-induced skin tests. However, oral terbutaline and parenteral ephedrine were shown to decrease the allergen-induced wheal.1
Cromolyn. Cromolyn inhaled or injected prior to skin tests with allergens or degranulating agents does not alter skin whealing response.1
Other drugs. Other drugs have been shown to decrease skin test reactivity. Among them, dopamine is the best-documented compound.1
Specific Immunotherapy. A decreased skin test reactivity has been observed in patients undergoing specific immunotherapy with pollen extracts, grass pollen allergoids, mites, hymenoptera venoms, or in professional beekeepers who are spontaneously desensitized. Finally, it was shown that specific immunotherapy in patients treated with ragweed pollen extract induced a decreased late-phase reaction.1
Adverse reactions include, but are not limited to urticaria; itching; edema of extremities; respiratory wheezing or asthma; dyspnea; cyanosis; tachycardia; lacrimation; marked perspiration; flushing of face, neck or upper chest; mild persistent clearing of throat; hacking cough or persistent sneezing.
1) Local Reactions
A mild burning immediately after injection is expected; this usually subsides in 10-20 seconds. Prolonged pain or pain radiating up arm is usually the result of intramuscular injection, making this injection route undesirable. Subcutaneous injection is the recommended route.
Small amounts of erythema and swelling at the site of injection are common. Reactions should not be considered significant unless they persist for at least 24 hours or exceed 50 mm in diameter.
Larger local reactions are not only uncomfortable, but indicate the possibility of a severe systemic reaction if dosage is increased. In such cases dosage should be reduced to the last level not causing reaction and maintained for two or three treatments before cautiously increasing.
Large, persistent local reactions or minor exacerbations of the patient’s allergic symptoms may be treated by local cold applications and/or use of oral antihistamines.
2) Systemic Reactions
Systemic reactions range from mild exaggeration of patient’s allergic symptoms to anaphylactic reactions.14 Very sensitive patients may show a rapid response. It cannot be overemphasized that, under certain unpredictable combinations of circumstances, anaphylactic shock is always a possibility. Fatalities are rare but can occur.5 Other possible systemic reaction symptoms are fainting, pallor, bradycardia, hypotension, angioedema, cough, wheezing, conjunctivitis, rhinitis,and urticaria.13, 14
Careful attention to dosage and administration limit such reactions. Allergenic extracts are highly potent to sensitive individuals and OVERDOSE could result in anaphylactic symptoms. Therefore, it is imperative that physicians administering allergenic extracts understand and prepare for treatment of severe reactions. Refer to “OVERDOSAGE” section.
1. Bousquet, Jean: “In vivo methods for study of allergy: Skin tests” Third Edition, Allergy Principles and Practice, C.V. Mosby Co., Vol. I, Chap. 19, pp 419-436, 1988.
2. Long, W.F., Taylor, R.J., Wagner, C.J., et al.: Skin test suppression by antihistamines and the development of subsensitivity, J. Allergy Clin. Immunol., pp. 76-113, 1985.
3. Holgate, S.T., Robinson, C., Church, Mike: Mediators of Immediate Hypersensitivity, Third Edition, Allergy Principles and Practice, C.V. Mosby Co., Vol. I and II, pp 135-163, 1988.
4. Wasserman, S., Marquart, D.: Anaphylaxis, Third Edition, Allergy Principles and Practice, C.V. Mosby Co., Vol. 1, Chap. 58, pp. 1365-1376, 1988.
5. Reid, Michael J., Lockey, Richard F., Turkeltaub M.D., Paul C., Platts-Mills, Thomas. “Survey of Fatalities from Skin Testing and Immunotherapy 1985-1989”, Journal of Allergy and Clinical Immunology, Vol. 92, No. 1, pp. 6-15, 1993.
6. Matthews, K., et al: Rhinitis, Asthma and Other Allergic Diseases. NIAID Task Force Report, U.S. Dept. HEW, NIH Publication No. 79-387, Chapter 4, pp. 213-217, May 1979.
7. Ishizaka, K.: Control of IgE Synthesis, Third Edition, Allergy Principles and Practices, Vol. I, Chap. 4, p. 52, edited by Middleton et al.
8. Nelson, H.S.: “The Effect of Preservatives and Dilution on the Deterioration of Russian Thistle (Salsola pestifer), a pollen extract.” The Journal of Allergy and Clinical Immunology, Vol. 63, No. 6, pp. 417-425, June 1979.
9. Seebohm, P.M., et al: Panel on Review of Allergenic Extracts, Final Report, Food and Drug Administration, March 13, 1981, pp. 84-86.
10. Rocklin, R.E., Sheffer, A.L., Grainader, D.K. and Melmon, K.: “Generation of antigen-specific suppressor cells during allergy desensitization”, New England Journal of Medicine, 302, May 29, 1980, pp. 1213-1219.
11. Seebohm, P.M., et al: Panel on Review of Allergenic Extracts, Final Report, Food and Drug Administration, March 13, 1981, pp 9-48.
12. Stevens, E.: Cutaneous Tests, Regulatory Control and Standardization of Allergenic Extracts, First International Paul-Ehrlich Seminar, May 20-22, 1979, Frankfurt, Germany, pp. 133-138.
13. Van Metre, T., Adkinson, N., Amodio, F., Lichtenstein, L., Mardinay, M., Norman, P., Rosenberg, G., Sobotka, A., Valentine, M.: “A Comparative Study of the Effectiveness of the Rinkel Method and the Current Standard Method of Immunology for Ragweed Pollen Hay Fever,“ The Journal of Clinical Allergy and Immunology, Vol. 66, No. 6, p. 511, December 1980.
14. Wasserman, S.: The Mast Cell and the Inflammatory Response. The Mast Cell-its role in Health and disease. Edited by J. Pepys & A.M. Edwards, Proceedings of an International Symposium, Davos, Switzerland, Pitman Medical Publishing Co., 1979, pp. 9-20.
15. Perelmutter, L.: IgE Regulation During Immunotherapy of Allergic Diseases. Annals of Allergy, Vol. 57, August 1986.
16. Bullock, J., Frick, O.: Mite Sensitivity in House Dust Allergic Children, Am. J. Dis. Child., pp. 123-222, 1972.
17. Willoughby, J.W.: Inhalant Allergy Immunotherapy with Standardized and Nonstandardized Allergenic Extracts, American Academy of Otolaryngology-Head and Neck Surgery: Instructional Courses, Vol. 1, Chapter 15, C.V. Mosby Co., St. Louis, Missouri, September 1988.